1. Field of the Invention
The present invention relates to a suppository, containing as its principal ingredient, a one-to-one complex of sulfamethoxazole and trimethoprim (hereinafter, to be referred to as SMX and TMP, respectively).
A pharmaceutical composition formed by mixing SMX with TMP has been known as an antimicrobial agent which performs an excellent synergetic action (See, for instance, U.S. Pat. No. 3,341,541). It still occupies an important status in the field of treating the particular infectious diseases caused by pathogenic bacteria resistant to other synthetic bactericidal agents and antibiotics. Though an old agent, it still has an irreplaceable importance in the field of chemotherapy.
2. Description of the Prior Art
However, such combination has a large dose as described in the U.S. Pat. No. 3,341,541 (for instance, SMX 800 mg+TMP 160 mg, per day) to make the oral administration difficult as well as to cause some damage to the stomach or duodenum through which this combination agent is absorbed. Therefore, the oral administration thereof is not necessarily easy.
Attempts have hitherto been made to solve the stated problem by administering the mixed preparation through coelomata, for example, the rectum, but a preparation formulated for this purpose by dispersing a simple mixture of SMX and TMP in a carrier has been found unsatisfactory because of its inherent disadvantages which will be stated below.
(1) During the manufacturing process:
In the mixing and kneading operation of the active ingredients with the carrier, the viscosity of the composition will rise abnormally so as to solidify, and this solidifying tendency will make the molding into the required dosage form very difficult.
(2) After preparation:
Uncontrollable variances in physical properties, for example, disintegration, dissolution and melting or softening point are inevitable. These will make the finished dosage form unpreferable from the practical point of view.
In addition to these disadvantages, even with a freshly molded preparation, the blood levels of each of the active ingredients after a predetermined period of administration cannot be attained as expected.
A proposal has been made to overcome these disadvantages in, for instance, German laid-open publication 2,415,660, wherein suppositories comprising two separate layers each containing carrier and one of the active ingredients, SMX or TMP, are disclosed. The separated layers may optionally be isolated further with an insulating layer composed primarily of carrier.
Although the proposed suppository might have overcome at least partly the difficulties ancillary to the manufacturing process, it is obviously inconvenient from the practical point of view because the manufacturing process includes at least two and in some instances three steps to obtain the finished product.